Clinical and genetic characterization of Netherton syndrome due to SPINK5 founder variant in Latvian population.
Journal
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology
ISSN: 1399-3038
Titre abrégé: Pediatr Allergy Immunol
Pays: England
ID NLM: 9106718
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
24
02
2023
received:
28
07
2022
accepted:
27
02
2023
medline:
28
4
2023
pubmed:
27
4
2023
entrez:
27
4
2023
Statut:
ppublish
Résumé
Netherton syndrome (NS) (OMIM:256500) is a very rare autosomal recessive multisystem disorder mostly affecting ectodermal derivatives (skin and hair) and immune system. It is caused by biallelic loss-of-function variants in the SPINK5 gene, encoding the protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI). Here, we describe NS clinical and genetic features of homogenous patient group: 9 individuals from 7 families with similar ethnic background and who have the same SPINK5 variant (NM_006846.4: c.1048C > T, p.(Arg350*)) in homozygous or compound heterozygous states, suggesting that it is a common founder variant in Latvian population. Indeed, we were able to show that the variant is common in general Latvian population, and it shares the same haplotype among the NS individual. It is estimated that the variant arose >1000 years ago. Clinically, all nine patients exhibited typical NS skin changes (scaly erythroderma, ichthyosis linearis circumflexa, itchy skin), except for one patient who has a different skin manifestation-epidermodysplasia. Additionally, we show that developmental delay, previously underrecognized in NS, is a common feature among these patients. This study shows that the phenotype of NS individuals with the same genotype is highly homogeneous.
Substances chimiques
Serine Peptidase Inhibitor Kazal-Type 5
0
SPINK5 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13937Informations de copyright
© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
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